Oral administration of quercetin and fisetin potentiates photocarcinogenesis in UVR-exposed hairless mice

Background: Phytochemicals have demonstrated great potential as photoprotectants. Apple-derived compounds such as quercetin, fisetin, and rutin are reported to provide topical photoprotection, but oral delivery has not been explored. Purpose: To determine the photoprotective effects of oral administ...

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Main Authors: Celina Pihl, Jonatan Riber Granborg, Fernanda Endringer Pinto, Peter Bjerring, Flemming Andersen, Christian Janfelt, Merete Haedersdal, Catharina Margrethe Lerche
Format: Article
Language:English
Published: Elsevier 2024-05-01
Series:Phytomedicine Plus
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2667031324000253
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author Celina Pihl
Jonatan Riber Granborg
Fernanda Endringer Pinto
Peter Bjerring
Flemming Andersen
Christian Janfelt
Merete Haedersdal
Catharina Margrethe Lerche
author_facet Celina Pihl
Jonatan Riber Granborg
Fernanda Endringer Pinto
Peter Bjerring
Flemming Andersen
Christian Janfelt
Merete Haedersdal
Catharina Margrethe Lerche
author_sort Celina Pihl
collection DOAJ
description Background: Phytochemicals have demonstrated great potential as photoprotectants. Apple-derived compounds such as quercetin, fisetin, and rutin are reported to provide topical photoprotection, but oral delivery has not been explored. Purpose: To determine the photoprotective effects of oral administration of quercetin, fisetin, and rutin, and their accumulation in skin assessed through mass spectrometry imaging. Study design: Groups of 25 hairless mice (n = 125 mice) received in the daily feed 100 mg/kg quercetin, fisetin, or rutin, 600 mg/kg nicotinamide in water as a positive control, or no supplementation as the UV control. The animals were exposed to ultraviolet radiation (UVR) equivalent to 3.5 standard erythema doses thrice weekly. Method: Mass spectroemetry imaging was used to assess local skin accumulation. Results: Oral administration of quercetin and fisetin reduced the time to tumour onset (Quercetin: second and third tumour [p < 0.045]; fisetin: third tumour [p < 0.021]), with no observed effect for rutin. Nicotinamide delayed the onset of all three recorded tumours (p < 0.0082). Results were supported by accelerated tumour growth following quercetin treatment (p < 0.0069), whereas nicotinamide reduced tumour growth (p < 0.00015). Skin accumulation of the compounds could not be demonstrated, suggesting other mechanisms must be explored to explain these effects on UVR-induced carcinogenesis. Conclusion: Oral administration of quercetin and fisetin to hairless mice increased UVR-induced tumour development. These results indicate a need for caution when selecting candidates for photoprotectants.
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spelling doaj.art-2cbaec1ac2ed464588504c15a954f79f2024-03-25T04:18:08ZengElsevierPhytomedicine Plus2667-03132024-05-0142100547Oral administration of quercetin and fisetin potentiates photocarcinogenesis in UVR-exposed hairless miceCelina Pihl0Jonatan Riber Granborg1Fernanda Endringer Pinto2Peter Bjerring3Flemming Andersen4Christian Janfelt5Merete Haedersdal6Catharina Margrethe Lerche7Dept of Dermatology, Copenhagen University Hospital – Bispebjerg and Frederiksberg, Copenhagen, Denmark &amp; Dept of Pharmacy, University of Copenhagen, 2400 Copenhagen, Denmark; Corresponding author at: Department of Dermatology, D92, Copenhagen University Hospital, Bispebjerg, Nielsine Nielsens Vej 17, 2400 Copenhagen, Denmark.Dept of Dermatology, Copenhagen University Hospital – Bispebjerg and Frederiksberg, Copenhagen, Denmark &amp; Dept of Pharmacy, University of Copenhagen, 2400 Copenhagen, DenmarkDept of Dermatology, Copenhagen University Hospital – Bispebjerg and Frederiksberg, Copenhagen, Denmark &amp; Dept of Pharmacy, University of Copenhagen, 2400 Copenhagen, DenmarkDept of Dermatology, Aalborg University Hospital, 9100 Aalborg, DenmarkDept of Dermatology, Aalborg University Hospital, 9100 Aalborg, Denmark; Dept of Dermatology, Private Hospital Molholm, 7100 Vejle, DenmarkDept of Pharmacy, University of Copenhagen, 2400 Copenhagen, DenmarkDept of Dermatology, Copenhagen University Hospital – Bispebjerg and Frederiksberg, Copenhagen, Denmark &amp; Dept of Clinical Medicine, University of Copenhagen, 2400 Copenhagen, DenmarkDept of Dermatology, Copenhagen University Hospital – Bispebjerg and Frederiksberg, Copenhagen, Denmark &amp; Dept of Pharmacy, University of Copenhagen, 2400 Copenhagen, DenmarkBackground: Phytochemicals have demonstrated great potential as photoprotectants. Apple-derived compounds such as quercetin, fisetin, and rutin are reported to provide topical photoprotection, but oral delivery has not been explored. Purpose: To determine the photoprotective effects of oral administration of quercetin, fisetin, and rutin, and their accumulation in skin assessed through mass spectrometry imaging. Study design: Groups of 25 hairless mice (n = 125 mice) received in the daily feed 100 mg/kg quercetin, fisetin, or rutin, 600 mg/kg nicotinamide in water as a positive control, or no supplementation as the UV control. The animals were exposed to ultraviolet radiation (UVR) equivalent to 3.5 standard erythema doses thrice weekly. Method: Mass spectroemetry imaging was used to assess local skin accumulation. Results: Oral administration of quercetin and fisetin reduced the time to tumour onset (Quercetin: second and third tumour [p < 0.045]; fisetin: third tumour [p < 0.021]), with no observed effect for rutin. Nicotinamide delayed the onset of all three recorded tumours (p < 0.0082). Results were supported by accelerated tumour growth following quercetin treatment (p < 0.0069), whereas nicotinamide reduced tumour growth (p < 0.00015). Skin accumulation of the compounds could not be demonstrated, suggesting other mechanisms must be explored to explain these effects on UVR-induced carcinogenesis. Conclusion: Oral administration of quercetin and fisetin to hairless mice increased UVR-induced tumour development. These results indicate a need for caution when selecting candidates for photoprotectants.http://www.sciencedirect.com/science/article/pii/S2667031324000253Ultraviolet radiationHairless miceSkin cancerOral deliveryPhotoprotectionPhytochemicals
spellingShingle Celina Pihl
Jonatan Riber Granborg
Fernanda Endringer Pinto
Peter Bjerring
Flemming Andersen
Christian Janfelt
Merete Haedersdal
Catharina Margrethe Lerche
Oral administration of quercetin and fisetin potentiates photocarcinogenesis in UVR-exposed hairless mice
Phytomedicine Plus
Ultraviolet radiation
Hairless mice
Skin cancer
Oral delivery
Photoprotection
Phytochemicals
title Oral administration of quercetin and fisetin potentiates photocarcinogenesis in UVR-exposed hairless mice
title_full Oral administration of quercetin and fisetin potentiates photocarcinogenesis in UVR-exposed hairless mice
title_fullStr Oral administration of quercetin and fisetin potentiates photocarcinogenesis in UVR-exposed hairless mice
title_full_unstemmed Oral administration of quercetin and fisetin potentiates photocarcinogenesis in UVR-exposed hairless mice
title_short Oral administration of quercetin and fisetin potentiates photocarcinogenesis in UVR-exposed hairless mice
title_sort oral administration of quercetin and fisetin potentiates photocarcinogenesis in uvr exposed hairless mice
topic Ultraviolet radiation
Hairless mice
Skin cancer
Oral delivery
Photoprotection
Phytochemicals
url http://www.sciencedirect.com/science/article/pii/S2667031324000253
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